Sukhbinder Dhesy-Thind

Clinical practice guidelines for the care and treatment of breast cancer: follow-up after treatment for breast cancer (summary of the 2005 update)

This article provides a summary of the changes along with the updated recommendations ([Table 1][1]) made by Health Canadas Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer to the article “Clinical Practice Guidelines for the Care and Treatment of

PANCREOX: A Randomized Phase III Study of Fluorouracil/Leucovorin With or Without Oxaliplatin for Second-Line Advanced Pancreatic Cancer in Patients Who Have Received Gemcitabine-Based Chemotherapy.

Purpose The standard of care for second-line therapy in patients with advanced pancreatic cancer after gemcitabine-based therapy is not clearly defined. The CONKO-003 phase III study reported a survival benefit with second-line fluorouracil (FU) and oxaliplatin using the oxaliplatin, folinic acid, and FU (OFF) regimen. 1 PANCREOX was a phase III multicenter trial to evaluate the benefit of FU and oxaliplatin administered as modified FOLFOX6 (mFOLFOX6; infusional fluorouracil, leucovorin, and oxaliplatin) versus infusional FU/leucovorin (LV) in this setting. Patients and Methods Patients with confirmed advanced pancreatic cancer who were previously treated with gemcitabine therapy and with an Eastern Cooperative Oncology Group performance status of 0-2 were eligible. A total of 108 patients were randomly assigned to receive biweekly mFOLFOX6 or infusional FU/LV until progression. Progression-free survival (PFS) was the primary end point. Results Baseline patient characteristics were similar in both arms. No difference was observed in PFS (median, 3.1 months v 2.9 months; P = .99). Overall survival (OS) was inferior in patients assigned to mFOLFOX6 (median, 6.1 months v 9.9 months; P = .02). Increased toxicity was observed with the addition of oxaliplatin, with grade 3/4 adverse events occurring in 63% of patients who received mFOLFOX6 and 11% of those who received FU/LV. More patients in the mFOLFOX6 arm withdrew from study due to adverse events than in the FU/LV arm (20% v 2%), whereas the use of postprogression therapy was significantly higher in the FU/LV arm (25% v 7%; P = .015). No significant differences were observed in time to deterioration on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 global health scale. Conclusion No benefit was observed with the addition of oxaliplatin, administered as mFOLFOX6, versus infusional FU/LV in patients with advanced pancreatic cancer previously treated with first-line gemcitabine.

Use of adjuvant bisphosphonates and other bone-modifying agents in breast cancer: A Cancer Care Ontario and American Society of Clinical Oncology clinical practice guideline

Purpose To make recommendations regarding the use of bisphosphonates and other bone-modifying agents as adjuvant therapy for patients with breast cancer. Methods Cancer Care Ontario and ASCO convened a Working Group and Expert Panel to develop evidence-based recommendations informed by a systematic review of the literature. Results Adjuvant bisphosphonates were found to reduce bone recurrence and improve survival in postmenopausal patients with nonmetastatic breast cancer. In this guideline, postmenopausal includes patients with natural menopause or that induced by ovarian suppression or ablation. Absolute benefit is greater in patients who are at higher risk of recurrence, and almost all trials were conducted in patients who also received systemic therapy. Most studies evaluated zoledronic acid or clodronate, and data are extremely limited for other bisphosphonates. While denosumab was found to reduce fractures, long-term survival data are still required. Recommendations It is recommended that, if available, zoledronic acid (4 mg intravenously every 6 months) or clodronate (1,600 mg/d orally) be considered as adjuvant therapy for postmenopausal patients with breast cancer who are deemed candidates for adjuvant systemic therapy. Further research comparing different bone-modifying agents, doses, dosing intervals, and durations is required. Risk factors for osteonecrosis of the jaw and renal impairment should be assessed, and any pending dental or oral health problems should be dealt with prior to starting treatment. Data for adjuvant denosumab look promising but are currently insufficient to make any recommendation. Use of these agents to reduce fragility fractures in patients with low bone mineral density is beyond the scope of the guideline. Recommendations are not meant to restrict such use of bone-modifying agents in these situations. Additional information at www.asco.org/breast-cancer-adjuvant-bisphosphonates-guideline , www.asco.org/guidelineswiki , https://www.cancercareontario.ca/guidelines-advice/types-of-cancer/breast .

Screening for Osteoporosis in Postmenopausal Women With Breast Cancer Receiving Aromatase Inhibitors: Less Is More?

Advancing age is associated with an increased risk of both breast cancer and osteoporosis. Aromatase inhibitors (AIs) are commonly used to reduce the risk of recurrence in postmenopausal women with early-stage, hormone receptor–positive breast cancer. Estrogen has favorable effects on bone, including stimulation of new bone formation, whereas it inhibits bone resorption through cytokine-mediated osteoclastogenesis. 1 AIs, by inducing an estrogen-depleted state, have been shown to have adverse effects on bone mineral density (BMD) and are associated with fracture rates that vary from 1% to 4%. 2-6 This is seen with both nonsteroidal (letrozole or anastrazole) and steroidal (exemestane) AIs. The use of tamoxifen in the comparator group complicates these studies, given that it functions as an estrogen agonist in bone tissue, thereby preserving bone density and increasing the difference in observed BMD compared with AIs. 7 After completion of treatment, fracture rates return to normal. 8 Markers of bone turnover are also significantly increased with AI treatment. 2-6 The recently reported bone mineral density substudy of the NCIC Clinical Trials Group, MAP.3, a trial of prophylactic exemestane in postmenopausal women at increased risk for breast cancer, provides clarification of the effects of AIs on BMD in the absence of a tamoxifen comparison group. 9 An absolute difference of 1.34% in

Canadian Institutes of Health Research dissemination grant on high-sensitivity cardiac troponin

a McMaster University, Hamilton, Ontario, Canada b Mayo Clinic, Rochester, MN, USA c Australian National University Medical School, Canberra, Australian Capital Territory, Australia d BHF/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK e University of British Columbia, Vancouver, British Columbia, Canada f Department of Emergency Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

18 F-fluorodeoxyglucose positron-emission tomography-computed tomography to diagnose recurrent cancer

Background:Sometimes the diagnosis of recurrent cancer in patients with a previous malignancy can be challenging. This prospective cohort study assessed the clinical utility of 18F-fluorodeoxyglucose positron-emission tomography-computed tomography (18F-FDG PET-CT) in the diagnosis of clinically suspected recurrence of cancer.Methods:Patients were eligible if cancer recurrence (non-small-cell lung (NSCL), breast, head and neck, ovarian, oesophageal, Hodgkin’s or non-Hodgkin’s lymphoma) was suspected clinically, and if conventional imaging was non-diagnostic. Clinicians were asked to indicate their management plan before and after 18F-FDG PET-CT scanning. The primary outcome was change in planned management after 18F-FDG PET-CT.Results:Between April 2009 and June 2011, 101 patients (age, median 65 years; 55% female) were enroled from four cancer centres in Ontario, Canada. Distribution by primary tumour type was: NSCL (55%), breast (19%), ovarian (10%), oesophageal (6%), lymphoma (6%), and head and neck (4%). Of the 99 subjects who underwent 18F-FDG PET-CT, planned management changed after 18F-FDG PET-CT in 52 subjects (53%, 95% confidence interval (CI), 42–63%); a major change in plan from no treatment to treatment was observed in 38 subjects (38%, 95% CI, 29–49%), and was typically associated with 18F-FDG PET-CT findings that were positive for recurrent cancer (37 subjects). After 3 months, the stated post-18F-FDG PET-CT management plan was actually completed in 88 subjects (89%, 95% CI, 81–94%).Conclusion:In patients with suspected cancer recurrence and conventional imaging that is non-diagnostic, 18F-FDG PET-CT often provides new information that leads to important changes in patient management.

Role of bone-modifying agents in metastatic breast cancer: An American Society of Clinical oncology-cancer Care Ontario focused guideline update

Purpose To update, in collaboration with Cancer Care Ontario (CCO), key recommendations of the American Society of Clinical Oncology (ASCO) guideline on the role of bone-modifying agents (BMAs) in metastatic breast cancer. This focused update addressed the new data on intervals between dosing and the role of BMAs in control of bone pain. Methods A joint ASCO-CCO Update Committee conducted targeted systematic literature reviews to identify relevant studies. Results The Update Committee reviewed three phase III noninferiority trials of dosing intervals, one systematic review and meta-analysis of studies of de-escalation of BMAs, and two randomized trials of BMAs in control of pain secondary to bone metastases. Recommendations Patients with breast cancer who have evidence of bone metastases should be treated with BMAs. Options include denosumab, 120 mg subcutaneously, every 4 weeks; pamidronate, 90 mg intravenously, every 3 to 4 weeks; or zoledronic acid, 4 mg intravenously every 12 weeks or every 3 to 4 weeks. The analgesic effects of BMAs are modest, and they should not be used alone for bone pain. The Update Committee recommends that the current standard of care for supportive care and pain management-analgesia, adjunct therapies, radiotherapy, surgery, systemic anticancer therapy, and referral to supportive care and pain management-be applied. Evidence is insufficient to support the use of one BMA over another. Additional information is available at www.asco.org/breast-cancer-guidelines and www.asco.org/guidelineswiki .

The Receptor for the CD200 Tolerance-Signaling Molecule Associated with Successful Pregnancy is Expressed by Early-Stage Breast Cancer Cells in 80% of Patients and by Term Placental Trophoblasts.

The CD200 tolerance‐signaling molecule that is expressed by a wide variety of tissues, including placental trophoblast and epithelial tumor cells, lacks an intracytoplasmic tail and must act by binding to CD200 receptors that have a limited expression on lymphomyeloid cells. This binding can inhibit inflammation and NK cells, promote macrophage secretion of indoleamine‐2,3 dioxygenase (IDO), and promote generation of Treg cells. Recently, CD200R1 was reported on human first trimester placental villous trophoblast cells. CD200R1 has not been described on malignant tumor cells. As malignant tumor cells exhibit a number of characteristics of trophoblast, is CD200R1 expressed?

Cardiac and Inflammation Biomarker Profile after Initiation of Adjuvant Trastuzumab Therapy

To the Editor: Liebetrau and colleagues have reported mechanistic data indicating that cardiac biomarkers appear rapidly in the blood upon induction of myocardial cell necrosis (1). Interestingly, concentrations of cardiac troponin T (cTnT)1 in both high-sensitivity (hs-cTnT) and fourth-generation assays continue to increase up to 1 day after the onset of necrosis. These data support the argument that irreversible myocardial injury causes prolonged release of cardiac troponin into the blood. Many anticancer therapies produce myocardial injury. Accordingly, measurement of blood cardiac biomarkers 1 day after therapy initiation may be necessary to assess whether irreversible myocardial injury has occurred. That may be important in the setting of trastuzumab treatment for human epidermal growth factor receptor 2–positive breast cancers, in which data have shown that this agent may cause cardiotoxicity, specifically a decrease in the left ventricular ejection fraction, which could lead to heart failure (2). Recent data have also suggested that inflammation (as assessed by C-reactive protein measurement) might be better than cardiac troponin I (cTnI) and the natriuretic peptides as a prognostic factor for the development of trastuzumab-mediated cardiotoxicity, although the cTnI assay used in that study was not a high-sensitivity assay (2). Moreover, earlier and additional inflammation biomarkers (as opposed to C-reactive protein) have also been demonstrated to identify the patients …

The CD200-tolerance signaling molecule associated with pregnancy success is present in patients with early-stage breast cancer but does not favor nodal metastasis.

The CD200‐tolerance signaling molecule prevents pregnancy failure and is also expressed by a wide variety of malignant tumors. The effect of CD200 mRNA expression on progression of human tumors has been variable.